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Seite: 28, Zeilen: 23-32
Seite(n): 253, 254, Zeilen: 253: last para - 254: col 1, lines 1-18
|The resident regulatory cells that develop in the thymus are generated in a burst of activity during the early stages of fetal and neonatal T cell development (Sakaguchi et al., 2001). They are polyclonal on the basis of diverse TCR usage (Shevach, 2002), and they are potentially capable of recognizing diverse self-antigens.
The promiscuous gene expression of many self tissue-specific proteins in the medullar epithelial cells of the thymus is described as a potential mechanism to ensure central tolerance to peripheral self-antigens, because this self-antigen expression in the thymus might lead, among other things, to the deletion of immature autoreactive T cells (Derbinski et al., 2001). However, it is possible that these self proteins are expressed at low levels and, additionally, by only some of the epithelial [cells, making clonal deletion a rather ineffective means of inducing tolerance to peripheral antigens.]
The resident regulatory cells that develop in the thymus are generated in a burst of activity during the early stages of fetal and neonatal T-cell
development7. They are polyclonal on the basis of diverse TCR usage3, and they are potentially capable of recognizing diverse self-antigens. Kyewski and colleagues8, have shown that messenger RNA transcripts encoding many tissue-specific proteins are expressed by ‘islands’of medullary epithelial cells in the thymus. It has been proposed that this promiscuous gene expression might be a mechanism to ensure central tolerance to peripheral self-antigens. Self-antigens that are expressed by these medullary epithelial cells in the thymus might delete immature self-reactive T cells. However, it is probable that these self-proteins are expressed at low levels and by only some of the epithelial cells, making clonal deletion a rather ineffective means of inducing tolerance to peripheral antigens.
7. Sakaguchi, S. et al. Immunologic tolerance maintained by CD25+CD4+ regulatory T cells: their common role in controlling autoimmunity, tumor immunity and transplantation tolerance. Immunol. Rev. 182, 18–32 (2001).
3. Shevach, E. M. CD4+CD25+ suppressor T cells: more questions than answers. Nature Rev. Immunol. 2, 389–400 (2002)
8. Derbinski, J., Schulte, A., Kyewski, B. & Klein, L. Promiscuous gene expression in medullary thymic epithelial cells mirrors the peripheral self. Nature Immunol. 2, 1032–1039 (2001).
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